Group C Neisseria meningitidis is the cause of a large percentage of bacterial meningitidis worldwide. Current measures to prevent this disease consist of vaccines composed of purified group C capsular polysaccharide. These vaccines are effective in adults but are poorly immunogenic in children. The poor results in infants is highly undesirable since this section of the population has the highest incidence of these infections.
The group C meningococcal polysaccharide (GCMP) is a weak immunogen and, hence, there have been efforts to enhance the immunogenicity of these polysaccharides to expand their usefulness as vaccines. One possible method of achieving this goal, which has shown some promise is by conjugation of these polysaccharides to a carrier, such as a protein.
Various investigators have isolated and purified intact capsular polysaccharides and have covalently coupled them to carrier proteins. These conjugates are more immunogenic than the polysaccharide alone. Many examples can be found in the literature which illustrate the success of these conjugate antigens. One such example, U.S. Pat. No. 4,673,574 describes the use of bacterial capsular polysaccharides conjugated to carrier proteins to form immunogenic compounds. Another example, U.S. Pat. No. 4,356,170 describes the immunogenicity of conjugates consisting of a specific polysaccharide, group A meningococcal polysaccharide (GAMP) coupled to a carrier protein. These conjugates provide an improved method for delivering effective levels of antigen to a host. The disclosures of both of these patents is incorporated in toto herein by reference thereto.
Another method for increasing immunogenicity has shown promise with the group B meningococcal polysaccharide (GBMP) antigens, as seen in U.S. Pat. No. 4,727,136. This method entails the replacement of N-acetyl groups of the sialyl moiety of the polysaccharide with N-propionyl groups followed by conjugation of the modified polysaccharide to a carrier protein. These conjugates are good immunogens and effectively cross-react with the native GBMP. This finding demonstrates that the addition of substituents onto the polysaccharide antigen can create additional immunogenic sites or epitopes for recognition by antibodies.
Vaccines which are currently prepared from O-acetyl-positive group C N. meningitidis are known to be poorly immunogenic. There have been reports that vaccine derived from an O-acetyl-negative variant is immunogenic. See Glode et al. The Journal of Infectious Disease Vol. 139, No. 1, January, 1979 pp. 52-59; Steinkoff et al, Infection and Immunity, October, 1981 pp. 144-146; and Arakere et al, Infection and Immunity, December, 1991, pp. 4349-4356.
Most group C N. meningitidis strains produce an O-acetyl positive (OAc+) polysaccharide in which the O-acetyl groups are distributed exclusively between C-7 and C-8 of its sialic acid residues. Amongst the known OAc-negtive (OAc-) strains is N. meningitidis group C MC 19 bacteria.
It is an object of the present invention to provide a highly immunogenic vaccine comprising a modified group C meningitidis polysaccharide conjugated to a carrier and also to provide a highly immunogenic vaccine containing the conjugate of a carrier and a modified polysaccharide derived from a OAc negtive variant.